Yet a 3rd Doctor's Opinion

About a week ago, I posted two doctors’ opinions on my condition. One was the Hepatologist Dr. Gish, the other, the Gastroenterologist Dr. Faris.

To refresh your memory, Dr. Gish said to see him in one year and we will see where I’m at as far as waiting for the 2011 release of Telepravir before treating again, as that seemed to be the logical thing to do after four failed treatments.

The Gastro’s take on this is to treat now with double-dosing of Pegasys along with 1200 mg Ribavirin. (something Dr. Gish first suggested).

Today, I saw my prior Gastro who had a whole different take on this. He looked at the same 2008 biopsy the other two doctors did and feels I’m working on 10% of my liver and to treat now could mean possible death. Not pleasant news I assure you. Why didn’t Dr. Gish mention this? I asked him, and his reply was that Dr. Gish will intervene at end stage liver disease with a transplant plan.

This is an emotional roller coaster ride for me. The former Gastro I saw today did say that he is going to attend an international conference re: Telepravir, and that he may be able to administer the real drug, not the placebo 9since they are in Phase III, in a new study here in Las Vegas.

I will email my concern of today’s meeting to Dr. Gish. The Gastro said he would not have treated me with the overdose of 24mcg of Infergen (which nearly killed me), instead he would not have even treated me with the typical 15mcg, but instead, would have treated me with less than 15mcg of Infergen, but raise the Ribavirin to 1600mg. He said he has had success with this plan in the past with 1a patients. Anyone have an opinion on all this?

Thanks,

Magnum

[Bill1954]

Hi Magnum,

I’ve been following your progress for years in here; sorry to hear you’ve been having so many problems with treatment.

I treated with CPMC in Sacramento; Geno 1, late stage 3 damage. I relapsed the first go around, and then re-treated with PEG-Intron and riba. I was able to use vials, and *emptied* the vials, getting around 204µg/week. I also used 2g (2000 mg) riba daily; although I never required epo, you might be able to manage quite a lot with Procrit/epogen. How did your HGB hold up in previous treatment attempts?

I wouldn’t like the plan Gish put together for you; I’d rather keep treating, but that’s me. I sure wouldn’t disregard his position either… he’s got a lot of whiskers in this business. I like the idea of taking the old GI’s plan, and running it through CPMC/Gish and see what he has to say. What do you lose by taking another stab at it with high-dose riba while you’re waiting?

Good luck, and let us know what Gish says—

Bill

[jmjm530]

First I would not weight two gastro's opinions against one hepatologist, especially one with the stature of Gish. That said, running what the gastro by Gish makes sense if for anything else to alleviate any unfound fears. I doubt very much that Gish is  holding anything back, and simply believes that Telaprevir is your best shot all things considered, but again can't hurt to ask. I would.

If you really want another opinion, and I think that reasonable, I would seek someone out at the Gish level. Someone like Dieterich, Afdhal, Schiff, Jacbosen, Donald Jensen, and a handful of others.

It was unclear from your post who the doctor was that treated you with the high dose of infergen. Was that Gish?

And yes, I have heard of using Infergen effictively in lower than standard doses but that really isn't going to help you moving forward.

-- Jim

[jmjm530]

The comment on  "isn't going to help moving forward" was partly based on an assumption that you relapsed on the higher dose of infergen so that doesn't seem to give you much of a chance on a lower dose. But now that I think of it, maybe you had to drop out because of side effects. So, depending on what your viral response was to the infergen and the reason for relapse, then a lower dose of infergen could help you, but again, my guess is that Gish is weighing the risks and rewards and feels that a PI in the mix is the best move. But again, no harm running it by him.

-- Jim

[Willy50]

I don't know if I mentioned it to you that there is a long shot chance that Telaprevir could be approved (ONLY for past TX failures) by the FDA this year.  The results of Prove 3 and a current efficacy and safety profile could be enough for them to allow the drug to be dispensed ONLY for past TX failures.  Vertex should provide the FDA this info by mid year and the FDA will decide yea or nay.  That is a possibility; I do not know how remote.  Even if they do not allow it there could be a looser leash for compassionate care for people who might not make it 2 years.

I still wonder if you could get a fibroscan and make sure that your staging is as the biopsy indicates, or any other measurement tool that allows you more data in making the hard decision.  I cannot help but wonder why this notion escaped Gish (and I don't think that it did).  All that I can say is that evaluating a biopsy is not always precise and the folks who interpret it may have a range of prognoses (or whatever the plural form of prognosis is... ; ))  Seems like I've heard people get told by a doctor to go get their affairs in order; 15 years later they are still kicking.  Unfortunately; the reverse is also true.  In lieu of additional testing Jim has in the past mentioned sending the slides to other doctors and getting an additional opinion.  Bottom line I doubt that Gish would neglect to mention it, nor would do so in order to sell you the whole enchilada combination plate; a liver transplant.  It is interesting in the variety of medical opinion one gets.  No wonder you are still asking and shopping.

My only real point in this....if I were to have an opinion (tell your Drs; "a carpenter that I met online says......" hahahahah  
That'll get their attention.  ; )

1) Gather Data like a fibroscan to look for nasty lobes that may skew biopsy interpretation.  (keeping in mind that fibroscan may not be a proven method but could round out biopsy interpretations)

2)  Gather Opinion.  Maybe more shopping for opinions. In short; can I wait?  Can I treat in 2 years?  I think that you should give more weight to the world class hepatologists opinion.

3  Risk assessment.   It may be a slippery slope but you may only have one more effective chance to cure.  Do the IR research and possibly pretreat the condition with diet/ excercise and metformin of DRs think it wise.  In the meanwhile the SVR rate should climb and the mechanisms of treating IR patients and past Tx failures will be far better understood than they are this week.  Long story short; your chances may be improving more rapidly than your liver staging is deteriorating.  IF you only have one great chance left make it count.

Disclaimer; none of us are doctors and this is an area where you need very informed advice.

I'm very interested, very hopeful for you.  I hope that you can come up with the best program.  It is worth shopping and carefully weighing all factors. It's a biggun.

best,
Willy

[portann]

Dear Magnum,

Sorry to hear that the third doctor is confounding the situation instead of confirming one option or the other.

I remember giving up reading Consumer Reports because the so-called 'best' product was determined by weighing many factors that didn't matter to me. So it was hard to know what was best for me.

I still think you should ask Dr. Gish to respond to now three distinct opinions. And yes, if you can muster the initiative, find someone with even more whiskers than Dr. Gish and set up a fourth consultation. It's worth it, given how these guys can drive patients around the bend with their d-amned differences of opinion.

Willy said something that made me wonder if Dr. Gish knows more about the availability of PI's off-trial sooner than publicized. He may have his ear to the ground, can't disclose this (even to a carpenter) and doesn't want to, in case it doesn't pan out.

Magnum, I'm thinking of you and sending you my best wishes. This has got to be tough.

Port

[HectorSF]

Magnum-

I hope this is helpful in some way. But it is only based on my own experience with these issues and I have no simple answers for you, as I am try to decide what I am going to do myself with the limited options I also am facing. Although somehow I do feel that somehow we will find a way as long as we keep hoping and trying our best to manage this illness as best we can each day.

I like Jim idea of trying to get an opinion from someone else at Gish's level. I also agree with Jim that you can't compare a heavy weight Hepatologist like Gish with any Gastro. Don't get me wrong, my Gastro is great, but he admitted that he doesn't know what my doctor at UCSF's transplant center knows. She works with HCV cirrhotics day in and day out. And treating HCV cirrhotics really it is a different ballgame. Anything that could cause us to decompensate… and our ONLY option is a transplant. And as you know in 5-10 years we become cirrhotic again with the new liver. So, please please whatever you do, be careful. We only have nine lives and we have used up most of them by this point as it is.

As a backup (if you haven't already done this) be in touch with a transplant center, just in case you do decompensate due to treatment. (If and when you treat). There is no hard data on the odds here but Hepatologists who commonly do transplants, think it is about 3-10%.

I guess it is up to what you feel most comfortable doing. If you can't wait then you can try higher dosage. If your former Gastro can get Telaprevir, personally I would do that. I think that would give you the best chance based on your history with the usual meds. I think you need a different way to attack the virus. PI.
I have been waiting for Telaprevir myself as a null responder. I think I saw that 43% of even null responders became undetectable by week 24 compared to probably 10% of us on SOC! But I have no platelets left myself now. 77k right now. So unless Promacta is not hepatotoxic, as the warning label says it is, I'm caught between a rock and a hard place.

Magnum, there are no easy, clear-cut way to go. It is about playing the odds. Nothing is guaranteed. I think you will know inside what to do when you finish your current weighing on opinions. We all are behind whatever your decision.

FYI-
Here is a link to a recent study showing responses due to varying dosages of Peg-Int and RIBA. Unfortunately this small study (76 patients) found that ribavirin only prevents relapse later in treatment. It doesn't reduce viral load during the first 24 weeks.

http://www.clinicaloptions.com/Hepatitis/Journal%20Options/Articles/Fried-Hepatology-2008/Capsule.aspx

Main Findings:
* HCV RNA decrease at Week 24 greater among patients who received high-dose vs standard-dose pegIFN
* No effect of higher RBV dose on virologic suppression through 24 weeks among patients receiving either 180 or 270 µg/week pegIFN alfa-2a
* Additional 0.3 log10 reduction in HCV RNA observed as early as Day 3 among patients who received high-dose vs standard-dose pegIFN, regardless of RBV dose received

Interested in what Gish says-

Best
Hectorsf

    

[pjhep80]

now you have me thinking again about trying SOC soon....i can always stop if its not working... i would still be considered as failed tx then right???

i posted before wondering if the PI's would be approved only for tx failed people but i believe my post was about if the insurance companies would pay for it along with riba and peg in TX naive people

i am tx failed (peg & virimadine phase iii trial) but i have no proof of this so im tx naive for all practical purposes...

[can-do-man]

Kinda surprized with the shape of your liver that Dr. Gish would think its best to wait  until 2011 maybe later to treat with telaprevir when there is trials now. I was dx with cirrhosis over 3 years ago. Geno1, relapser. When both these PI trials came open i sought out advice on whether to tx now or wait.

My hepatologist, Doctor Dieterich, and a GI that treats hep c thought it would be wise for me to treat now.. Also when i asked Dr. D between telaprevir and boceprevir his thoughts was these latest phase 3 trials would be the deciding factor and he has every day hands on with both drugs. FROM DR. D
--------------------------------------------------------------------
There is some anemia from bocepravir and of course the treatment is longer for the most part, 12 months vs 6 months. There is no free lunch because as you state there can be a rash with telapravir.  We really don’t know all the details until both phase 3’s are completed. Good luck!

  

  

Douglas T. Dieterich, M.D.

Professor of Medicine

Director of CME, Department of Medicine

Director of Outpatient Hepatology

Division of Liver Diseases

Mount Sinai School of Medicine

Annenberg 21-42

New York NY 10029

212 659 8877

Fax [phone]
-----------------------------------------------------
Also i'm thinking i read where you were told the SVR rate for NON- RESPONDERS was 75%, not according to vertexs latest results, nor boceprevirs.

Vertex Reports 52% SVR 12 Rate for a 24-week Telaprevir-based Regimen in Genotype 1 Hepatitis C Patients Who Failed Prior Treatment.

Undetectable HCV-RNA by Response to
Prior Peg-IFN/RBV Treatment  
Week 12  Week 24
(end of treatment) SVR 12
(week 36; 12 weeks post-treatment)
Non-responders (n=66) 71% 65% 41%
Relapsers (n=40)  88% 83% 73%
Breakthroughs (n=9) 44% 44% 44%
Total (n=115)  75% 70% 52%

http://www.hivandhepatitis.com/hep_c/news/2008/061308_c.html

Their study shows svr rates for non-responders was 41%, also this trial did not include us with cirrhosis, which i would think would have brought the SVR rate even lower. As for shorter tx time that is passed around, not to sure for us hard to tx geno1's, If this latest vertex trial with longer arms shows better SVR rates then i would think it would be in our best interest to tx longer, i know i'm hoping i'm in the 48 week arm over the 36 week one.

After 10 times, i really hope for the best for you........Stay well

cando

[FlGuy]

Tough decisions all around, Magnum. I would do just about anything to avoid a transplant scenario and you are alreday getting banded.  TVR, as pointed out by Doc3 and Willy are not sure bets for availabilty before public roll-out. Doing nothing does not seem to be an option.  Have you asked any, or all three, if there is any forstalling continuing damage value in either a maintenance dose of Peg or Infergen?.  It seems like time is the immediate enemy right now.
As I mentioned in a prior thread and a private message to you, there is another place for an additional opinion.
On (I hope) a lighter side....Willy wrote "a carpenter that I met online says......" .  I really hope that Willy is a carpenter because I know that Bill is and tht Bill's post preceded Willy's in this thread.
Like Bill and many others here, I keep track of your adventures and progress and always wish the best for you.

[susan400]

You could contact another hepatologist as was suggested above and send your slides.  If you have any sort of religious faith, you could pray about your decision, which has often helped me in making critical decisions.  I, personally, have treated so many times because I'm terrified of going through a transplant.  Of course, I don't have cirrhosis yet, so, I have a little bit longer to get to that point.  I'm at Grade 2 Stage 3, 7 yrs of bridging fibrosis.   I think if I didn't want to seek out another opinion, if it were me, I'd probably take a chance with doing the lower dose of interferon and higher Riba.  I did higher Riba at 1600 at day, for me, for my body weight at that time, it was quite a bit higher dose.  I used the Procrit for my anemia.  Your decision is so hard and I certainly don't envy you any, having to make such a difficult decision.  I wish you all the best and please keep us up to date with what you decide!!

Susan400

[Willy50]

That is funny.  I didn't know Bill was a carpenter too, but then that would explain why he knows so much about HCV.  ; )   I'm not even a good carpenter, but I had to stick some trade in there to make the joke work.

So far as the chances with Vertex I still don't think that we have seen what a 4 week lead in will do for the results.  I believe that Vertex has also decided to do some longer treatments for the slower responding patients and a longer treatment period may help but I think that much of it is determined in the initial 12 weeks.

We ultimately will see cocktails being built for the treatment of HCV but I wonder if it might be worth doing a few things to try to bring the viral load down before hitting it with the TVR,   Pre-dosing is one method with a 4 week SOC lead in.  Unfortunately the results on that will not be out (for Vertex anyway) for a spell since that trial just commenced in the fall.  Obviously Scherring-Plough thought it was a good idea and they seem to have had decent eifficacy rates with it in a compound which does not seem to be as powerful.  Alinia is another easily prescribed drug which might also help bring the viral load down Pre-PI dosing.  There is beginning to be compelling evidence that pursuing the IR (insulin resistance) issue could also yield a higher response rate if it were an issue.  

I agree with what Mike Simon wrote in the other thread...... that it might be possible to determine in 4 weeks (not 12) whether SOC would work.  I guess I would ask if one could tell if a hybridized SOC could work in the same amount of time if there is a question as to if you can wait. That could involve Metformin and or alinia and higher starting dose of SOC.  I would think that one could assess ones odds at 4 weeks.  Even if it were not successful it might provide some groundwork for attempting a similar "run" with TVR added in 2 years.  You may have the viral kinetics which may predict whether PI will be sufficient when you treat.  What would you be out in trying?
I wonder if in your old treatments you have enough data to compare if these few additions could turn the tide?  Also of note Cocksparrow is doing a "pimped out" version of TX and will soon have a 4 week result that will be of interest to us all and possibly to a doctor you are consulting with.  You may also have EASL results in one month that could shed some light on some of the conversation here.  If Vertex has anything of note to share with the community it will be at EASL in Mid April.

best,
Willy

[justme53]

As a cirrhotic, I'm anxiously awaiting the quick availability of PI in the not too distant future, but even more so am I looking forward to the possibility of a rescue drug, potentially Eltrombopag (or variation thereof) to keep us in the game. I'm soon coming off 12 weeks of double dosing and my platelets were the first to start dropping. I did read somewhere about the possibility of titering UP with the Peg with thrombocytopenia, but can't find the link right now.

Not trying to sound negative in the least, but all the great results we're seeing with the PI's won't mean jack to us if we can't tolerate it long enough to get results.

http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/Thrombocytopenia.aspx

Pam

[nygirl7]

Magum,
As someone who's seen for years all that you have had to deal with I just wanted to say something you full well know, all of us are with you.

At this point with so many differing conflicting opinions I too believe seeking out another top level heppo probably is in your best interest, there are just so many "If's" in your situation right now that their opinions differ even more than ours would!

I can tell you if you can get to NY that Jacobson was one of the nicest most caring intelligent human beings I've ever had the privilege to meet. And he was completely honest with everything that he had to say to me.  His second opinion changed everything for me and I believe enabled me to get to SVR. At that time he was already light years ahead of what other doctors knew and because he is so at the forefront of doing the investigative work on the big studies........he knew exactly what was coming down the pike and had some ideas back then that were kind of radical for the time.

I don't know the other docs but just wanted to reiterate how totally qualified a person I found him to be. Plus he called my GI right away and told him he would be available for anything he needed on my case and would consult with him for free. Pretty bizarre in this day and age huh?  I could see how much he cared and how much he truly wants all us heppers to be cured.

I thought that last part might be useful to you - I lived IN NY and he was willing to do it so certainly I am sure 100% he would do it for someone who did not.

All of my best to you.........you know we will be watching and praying and sending all good thoughts your way.

[mikesimon]

You wrote:
"And as you know in 5-10 years we become cirrhotic again with the new liver."

From my reading roughly  20% of HCV transplant recipients who do not achieve SVR will become cirrhotic within 5 years of transplant. Of those who do treat roughly 30% will achieve SVR. I don't know about the 10 year rate of cirrhosis for HCV transplant recipients but I seriously doubt it is 100%. In fact I know a man transplanted in 1996 for HCV genotype 1b who never treated and in not cirrhotic as of last September. In fact he is quite healthy. Transplants for HCV do have a hard road but it serves no one to portray it as worse than it is. I don't think anyone goes into transplant believing it is a panacea or a cake walk. I am 9 years post transplant in June, genotype 1b,  SVR since June 2004 and my stage is mild to moderate fibrosis. There can be a good result.

Regarding your statement
"But I have no platelets left myself now. 77k right now."

I treated for 73 weeks with a platelet count in the low 20,000s at many points during treatment and never higher than 70,000. I don't know the protocol for the PI trials so perhaps a count of 77,000 excludes participation. I do, however, know of several people who have treated successfully with SOC and had platelet counts significantly lower than 77,000.

I have little to offer but, without compelling reason(s) to the contrary, I would give considerably more weight to Gish's reading of your biopsy. It is hard for me to imagine that he misread or understate your biopsy slides to the extent suggested by this latest GI. The fact that Gish may be closer to a transplant center and have more experience with transplantation doesn't suggest to me that he'd downplay or understate your biopsy results. That just sounds very wrong to me.

Whatever way you go I wish you the very best Magnum.

[portann]

This sounds corny but Mike's comments really cheered me up about your situation. Thanks, Mike.

I had no idea that a person can treat successfully with platelet counts in the low 20,000's.

Given this, I'd want to be in the most experienced hands possible and go for it.

My gut feeling is for Gish or another top guru. Is there anyone you 're leaning towards for a fourth consultation?

All the best and thinking of you,

Port

[Willy50]

one digression, at least kinda and an additional thought.

So far as looking at the worst case scenario, if you were unable able to clear, you might face a liver transplant.  As mentioned, liver transplants have a kind of double whammy; if you are still infected the anti-rejection drugs make it harder to clear the virus since they diminish immune response.  I think that in the future this will be less of a problem since newer therapies will enable a much larger group of those transplanted to be cured.  On the other side of the pond those same therapies will diminish the need for livers and the pool of available livers may increase.  

I just want to make the point (again, ad-nauseum, I admit) that given the likelihood of resistance with PI's you will need to put your very best foot forward when you use them.  I still don't know if this is *known* yet.  I still wonder if after a period of time the virus might reset to default and a new swing at it could be taken with either a PI or a PI with another compound which renders it a more potent combo, perhaps trumping the resistance issue.
-----------------
A separate issue but IF one did the HOMA test and determined that IR was an issue...... and took dietary steps or medications to improve that issue...... might this help arrest ones continued progression towards decompensation?  I don't know the answer but thought that if it could make a difference it could factor into ones decision.  Since this issue is only on the cutting edge of discovery right now this could be an area where there is not much data but it could factor in.  I'm not knowledgeable but thought I'd throw it into the mix.

Willy

[jmjm530]

From my own experience, and in part from what I read here, the more credentialed the doctor, the less of a tendency to paint let's call it a picture of gloom. Be it in interpreting biopsy results, or blood results. The platelet example Mike gave is one example. Another example are docs reducing the Peg dose too early based on what they consider low WBCs and ANC. That's why, especially if you have significant liver damage, it's important to see someone with a deep patient load of similar patients so that you will be able to get the best possible perspective. Personally, I would look at the Gish consult as perspective 1, not perspective 3. Going for one or two more seems reasonable as the decision literally will be made to a great extent under the microscope.

-- Jim